Inhibition of cardiolipin biosynthesis in the hypoxic rat heart

Abstract

Cardiolipin is the principal polyglycerophospholipid in the heart. The effect of hypoxia on cardiolipin biosynthesis was investigated in isolated rat hearts perfused in the Langendorff mode. Hearts were pulsed-labeled for 60 min with 0.1 mM [1,(3)-3H]glycerol in Krebs Henseleit buffer saturated with either 95% O2/5% CO2 (control) or 95% N2/5% CO2 (hypoxic). Radioactivity incorporated into phosphatidylglycerol and cardiolipin were reduced 88% (P < .05) and 79% (P < .05), respectively, in hypoxic hearts compared to controls. In other experiments, hearts were pulse-labeled for 15 min with 1.4 mM [32P]Pi in Krebs Henseleit buffer saturated with 95% O2/5% CO2 and subsequently perfused for 60 min under control or hypoxic conditions. The radioactivity incorporated into CDP-1,2-diacyl-sn-glycerol, phosphatidylglycerol, and cardiolipin were reduced 61% (P < .05), 71% (P < .05), and 70% (P < .05), respectively, in the hypoxic hearts compared to controls, indicating a decreased formation of CDP-1,2-diacyl-sn-glycerol in the hypoxic heart. The activities of the enzymes involved in cardiolipin biosynthesis and the cardiac pool sizes of cardiolipin, phosphatidylglycerol, and CDP-1,2-diacyl-1,2-diacyl-sn-glycerol were unaltered between hypoxic and control hearts. In contrast, cardiac adenosine-5'-triphosphate and CPT levels were decreased 94% (P < .05) and 92% (P < .05), respectively, in hypoxic hearts compared to controls. We postulate that the biosynthesis of the cardiac polyglycerophospholipid cardiolipin may be inhibited by a decreased adenosine-5'-triphosphate and cytidine-5'-triphosphate level in the heart.